Our studies are continuing to focus on defining the early events in coxsackievirus infections. We have provided evidence, by receptor competition, that many prototype picornaviruses sort into the subgroups in which they were classified originally by disease production and histopathology. We propose to evaluate the dual functions of receptors to attach and eclipse coxsackeiviruses and our multicomponent receptor hypothesis. We are continuing our efforts to purify and characterize the membrane receptor (R1) which binds the prototype group B coxsackievirused to HeLa cells. This receptor will be compared to a second receptor (R2) which will be purified from RD cells and to a third receptor (R3) obtained from human O erythrocytes. Monoclonal antibodies to the different receptors also will be prepared and utilized as probes to help characterize and isolate the receptors. RD cells select hemagglutinating (HA+) group B coxsackievirus variants (host range mutants) from HA- populations. Since HA+ variants produce a modified histopathology and minimal disease in mice, it will be important to determine the role of the different receptors in virulence. Our studies of differentiating myogenic rat cells (L8) in culture have shown that coxsackieviruses of group A and B3 will bind to separate receptors on non-fusing cells, but are not eclipsed until the cells are capable of fusion. Plans are made to determine whether eclipse is mediated by: (1) accessory factors or (2) a rearrangement of receptors during differentiation. It is anticipated that the results will determine the adegree of homology between receptors for the group B coxsackeiviruses and determine those early events in virus-cell interactions which may be associated with avirulence or virulence of selected virus strains.